Clinically, type 1 diabetes (T1DM) and high-level type 2 diabetes (T2DM) patients require various everyday insulin infusions to keep up with blood glucose levels, which might cause incredible agony, is a bother to patients, and can prompt hyperinsulinemia. In comparison, oral insulin treatment is very consistent.
There are two bottlenecks in accomplishing the desired oral insulin treatment. One is the gastrointestinal boundary that generally limits the oral retention of insulin; the other is the lack of amassing of insulin at target sites after ingestion. Under physiological circumstances, the liver is exposed to a 2–3 fold higher insulin level than the rest of the body and is liable for discarding close to 33% of ingested glucose. Hence, oral insulin conveyance is necessary to stepwise cross the digestive mucosal boundary and explicitly focus on the liver, accordingly mimicking the biodistribution of endogenous insulin and at last improving the use of blood glucose.
In a review distributed in Nature Correspondences, Prof. Gan Yong’s group from the Shanghai Institute of Materia Medica (SIMM) of the Chinese Institute of Sciences, as a team with Prof. Wei Pack from Fudan College, detailed a multifunctional nanocarrier looking like a viral surface for oral insulin treatment.
The researchers designed a ligand-switchable nanoparticle (Energy/Lady PNPs) with a pH-responsive stretchable cell-entering peptide (Kick) and a liver-focusing on moiety (Lady).When taken orally, acidic conditions cause Kick to spread from the surface in an infection-like manner, allowing Energy/Lady PNPs to effectively cross digestive barriers.As a result of Kick collapsing at physiological pH, Lady was exposed, allowing the specific focusing of energy/Lady PNPs to the liver.
Kick/Lady PNPs demonstrated strong digestive retention and hepatic affidavit (representing 79.1% of total out assimilation) in vivo.Also, the insulin-stacked Kick and Lady PNPs showed huge hypoglycemic impacts in type 1 diabetic rodents. Vitally, they expanded hepatic glycogen creation by 7.2 percent, further developing glucose digestion.
This review provides a clever oral insulin conveyance system that effectively bypasses the digestive mucosal boundaries and precisely targets the liver by mimicking novel surface elements and infection elements, achieving sane removal of blood glucose in diabetes and contributing to maintaining blood glucose homeostasis.
More information: Tiantian Yang et al, Ligand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy, Nature Communications (2022). DOI: 10.1038/s41467-022-34357-8
Journal information: Nature Communications
